High viscosity embolizing compositions comprising prepolymers

• US 7,459,142 B2
• Filed: 06/06/2002
• Issued: 12/02/2008
• Est. Priority Date: 06/06/2002
• Status: Expired due to Term

• Current Assignee: Covidien LP (Medtronic Plc)
• Original Assignee: Micro Therapeutics, Inc. (Medtronic Plc)
• Inventors: Greff, Richard J.
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US10/162,653
• Publication Number:
  US 20030228273A1
• Time in Patent Office: 2,371 Days
• Field of Search: 424/1.11, 424/1.25, 424/1.65, 424/9.1, 424/9.3, 424/1.29, 424/1.33, 424/1.37, 424/400, 424/422, 424/423, 600/3, 600/4
• US Class Current: 424/1.25
• CPC Class Codes: A61K 31/78 of acrylic acid or derivatives thereof
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 49/0409 Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is not a halogenated organic compound
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61L 24/001 Use of materials characterised by their function or physical properties
• CPC Class Codes: A61L 2430/36 for embolization or occlusion, e.g. vaso-occlusive compositions or devices artificial blood vessels A61L27/507
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

Disclosed are novel high viscosity compositions for embolizing blood vessels which comprise a biocompatible prepolymer and a contrast agent, and optionally a thickening agent and/or a biocompatible solvent. Also disclosed are methods for embolizing a vascular site by injecting high viscosity prepolymer compositions into said site. The disclosed compositions and methods are particularly well suited for the treatment of aneurysms.

Claims

1. A method for embolizing a vascular site, said method comprising:

(a) selecting an embolic composition comprising

a cyanoacrylate prepolymer and/or partially reacted monomers and oligomers thereof;

a biocompatible contrast agent, in an amount capable of being monitored during injection; and

a thickening agent which is a polyacrylate polymer,

wherein the viscosity of said composition prior to injection is at least about 150 centistokes at 40°

C.;

(b) transferring the embolic composition to a delivery catheter having a proximal end and a distal end, wherein the distal end of the delivery catheter is positioned at the vascular site to be embolized; and

(c) injecting the embolic composition into said vascular site in sufficient amounts to embolize said vascular site.

2. The method according to claim 1, wherein the embolic composition further comprises a biocompatible solvent.

3. The method according to claim 1, wherein said composition has a viscosity of at least 200 centistokes at 40°

C.

4. The method according to claim 1, wherein said composition has a viscosity of at least 500 centistokes at 40°

C.

5. The method according to claim 1, wherein said composition has a viscosity of from at least 500 to 5,000 centistokes at 40°

C.

6. The method according to claim 1, wherein said biocompatible contrast agent is a water insoluble contrast agent.

7. The method according to claim 6, wherein said water insoluble contrast agent is selected from the group consisting of tantalum, tantalum oxide, tungsten, barium sulfate, gold, and platinum.

8. The method according to claim 7, wherein said water insoluble contrast agent is tantalum.

9. The method according to claim 1, wherein said biocompatible solvent is selected from the group consisting of ethyl lactate, dimethylsulfoxide, ethanol, acetone, ETHIODOL®

, LIPIODOL®

, iodinated poppy seed oil, iodinated soy bean oil, water, and hexamethyldisiloxane.

10. The method according to claim 1, wherein said thickening agent is polymethyl methacrylate.

11. The method according to claim 1, comprising an additional step of (a′

) heating and mixing the embolic composition of step (a) to at least 40°

C. to form a uniform suspension;

and wherein the material transferred in step (b) is the uniform suspension of step (a′

).

12. The method according to claim 11, wherein the composition transferred is maintained at a temperature above 40°

C.

13. The method according to claim 1, wherein, prior to the embolic composition being injected, a blood flow attenuating device is inserted immediately upstream the ejection port of said catheter.

14. The method according to claim 13, wherein said blood flow attenuating device is an inflatable microballoon which permits both normal and attenuated blood flow depending upon whether the microballoon is deflated or inflated.